PROJECT SUMMARY/ABSTRACT The candidate, Dr. Ashley Henneghan's long term career goal is to develop effective therapeutic treatment approaches to reduce or prevent self-reported cancer related cognitive impairments (sr-CRCI), through collaborative multi-disciplinary research that integrates neuroimaging data, specifically related to sr-CRCI. Current gaps in the literature make it difficult to understand the mechanisms of sr-CRCI, how sr-CRCI is similar or different to psychological distress, and what predicts the incidence of sr-CRCI following cancer treatment. To continue progress towards her overarching career goal, the candidate will longitudinally examine sr-CRCI, brain connectivity (using functional magnetic resonance imaging), and psychological distress, from pre-surgical baseline to 1-year post treatment in a cohort of 89 breast cancer survivors and 50 matched controls. Three specific research aims are proposed in a retrospective longitudinal study to (1) determine the differences in brain connectivity among BC survivors with high sr-CRCI, BC survivors with low sr-CRCI, and healthy controls, (2) compare brain connectivity patterns among groups of survivors based on distress severity, and (3) explore models of sr-CRCI, psychological distress, and brain connectivity in BC survivors. The candidate's previous training and research experience have prepared her to undertake this research, but she requires continued mentorship in four critical areas to complete the proposed project and achieve her career goals. An expert multi-disciplinary mentor team has been selected to oversee Dr. Henneghan's training and progress towards her short term goals for this K01 proposal to (1) gain knowledge and skills in conceptually using fMRI data in cognitive research specifically related to connectomics, (2) develop proficiency in longitudinal research design and methods, (3) increase knowledge of breast cancer etiology and treatment, and (4) enhance and refine skills requisite for a successful career as an independent investigator. Training and research activities for this K01 proposal will focus on conducting a secondary retrospective data analysis of the candidate's Primary Mentor's longitudinal study of a cohort of BC patients and healthy controls (R01CA172145). The facilities and other resources at the University of Texas at Austin provide the collaborators of this proposal with a rich environment that is supportive of scientific research and a history of successful collaborative research in the areas of cancer and cognition. The project addresses a high priority of the NINR strategic plan to explore the mechanisms underlying symptoms of illness and developing personalized treatments that address these mechanisms through symptom science research. The K01 Award would provide a vital opportunity for protected time to enhance the candidate's skills and gain the necessary training and expertise in order to conduct the proposed study and apply the findings to a new investigator R01 proposal. The candidate is committed to a long career as an independent oncology researcher with a focus on symptom science.